The FDA Might Pull The Only Treatment for a Rare Form of Muscular Dystrophy

The disease is so severe that most people with it don't live past their 20s.

Eight-year-old Pietro Scarso thought it was a Saturday when he woke up in his Staten Island home one morning last year. The weekend meant no school. Excited, he ran down the hallway in nothing but his underwear, unaware that it was actually a Wednesday.

"That's really, really fast for him," Pietro's mother, Dayna, tells me. She's playing a video of the moment she recorded on her phone. "He just woke up and started running, lightning speed."

Just a year earlier, Pietro couldn't walk long distances, climb stairs, or even step up on a curb. He needed help getting in and out of spaces like cars and pools. Now, Dayna and her husband, Manni, say that's all changed. He uses the elevator in their home far less frequently, and doesn't ask for help out of the car as often as he once did.

The couple attributes the improvement to eteplirsen, a drug that's been shown to improve the ability to walk in boys who have Duchenne muscular dystrophy (DMD), a rare and fatal muscle-wasting disease. On May 3, less than two weeks before his eighth birthday, Pietro will complete a 96-week safety study for eteplirsen. Since the US Food and Drug Administration granted the drug accelerated approval on September 19, Pietro and the other participants will continue to take eteplirsen after the trial ends. (Thankfully, their insurance—as with many of the children in the study—covers the nearly $300,000 annual cost of the drug.)

The FDA's approval, however, comes with several conditions. If the two-year study that eteplirsen's manufacturer, Sarepta Therapeutics, just completed does not satisfy the FDA's efficacy standards, the agency could pull eteplirsen from the market—something it's done to a few dozen other medicines before in similar situations. That would have a considerable financial and emotional impact on families like the Scarso's since eteplirsen is the only drug currently available on the market that treats Duchenne directly.

"It's hard because we know what's waiting around the corner. We know what's in store for him," Pietro's father, Manni, told me a few months before eteplirsen was approved. Duchenne muscular dystrophy is caused by the absence of the muscle protein dystrophin, which is linked to the X chromosome. Boys with DMD begin to lose motor function at three years old. (Pietro was first diagnosed in 2012, a few months before his third birthday). Many boys start to use wheelchairs between the ages of seven and 12; since the disease is so severe, most men don't live past their 20s.

To treat DMD, many parents put their boys through a regimen of steroids, anti-inflammatories, and physical therapy. Combined, they can help slow down the disease; steroids can maintain muscle strength, while regular stretching can help prevent muscles and tendons from tightening. At most, however, they address the symptoms—not the condition.

That's what makes eteplirsen extraordinary, advocates say. Boys missing specific sections of dystrophin, known as exons, undergo a weekly liquid infusion to help coax muscle fibers to create a functional, albeit truncated version of dystrophin. Eteplirsen is only effective, however, if patients are missing a specific exon—known as exon 51—which is true in about 13 percent of cases, according to the Muscular Dystrophy Association. Pietro is among that 13 percent.

Dayna says that Pietro has been "really stable" since starting the trial last July. "Everything has been on the up and up," she says. "[It's] doing exactly what the drug is supposed to do—slow the progression of the disease."

As much as eteplirsen has done for Pietro, however, the drug has been marred in controversy since late 2013, when the FDA required Sarepta to conduct a larger phase III study in order for it to even consider an application for approval. Early trials showed eteplirsen produced a substantial amount of dystrophin with few side effects, allowing boys to walk longer in a six-minute walk test. But subsequent tests showed it actually produced a much smaller amount than they thought. The FDA also questioned the drug's safety profile, though it showed few adverse effects. These concerns led the administration's advisory committee to vote against approval, despite acknowledging that the drug worked to some extent. The FDA later overruled that decision to push eteplirsen through its Accelerated Approval program, which fast-tracks treatments for rare conditions that have an unmet need.

Admittedly, Sarepta's initial study had some flaws, says Pat Furlong, founding president and CEO of Parent Project Muscular Dystrophy. The participant pool was small, and the study itself wasn't "as rigorous" as advocates would have liked, she says. But Duchenne is also rare, which means the patient population is inherently small—just one in 3,500 boys is born with DMD. It also means that historical data is limited compared to more common conditions like breast cancer or arthritis. That shouldn't discount what eteplirsen has been shown to do, both through scientific studies and anecdotal reports, Furlong says. Nor should it dismiss what the community will learn about long-term effects by starting more boys on the drug.

"I've been in this field for 30 years, and I can say that having a gateway, having an approval, having a mean change in dystrophin, I hope that means something—and I believe that it does," Furlong says, "It's only in looking down the road, because of the chronicity of this disease, that we're going to know definitely." (An FDA spokesperson declined a request for an interview.)

For parents and advocates, the issue is less about eteplirsen's ability or inability to produce dystrophin in extraordinary numbers. Instead, they're more concerned with whether or not the drug can improve a person's quality of life. Even the smallest amount of dystrophin will help a boy with DMD move in ways they couldn't before, they argue. "Is he running faster or popping higher? I don't think so," Dayna says of Pietro. "But he's running and popping. He's still doing that. That's all we really want right now."

Critics of eteplirsen are skeptical about its benefits. Many have suggested that the improvements parents report are the result of a "placebo effect" and not due to the drug's efficacy. If in two years the drug proves to be "300 grand worth of placebo," as one skeptic wrote on his blog, that would mean a multibillion dollar hit to investors, not to mention the loss of hundreds of thousands of dollars that families would've spent. The FDA approval process is there to protect against these health and financial risks.

But to chalk all of the benefits up to the placebo effect betrays a fundamental misunderstanding of how Duchenne works, argues Christine McSherry, founder and executive director of the Jett Foundation,a Massachusetts-based nonprofit dedicated to Duchenne advocacy and research.

"When you see a child who couldn't feed themselves on week one and then is feeding themselves on week nine, that is a change from baseline that is not placebo," McSherry says. McSherry's son Jett was also enrolled in an early eteplirsen trial; four years later, the 20-year-old has shown increased arm, hand, back, and leg strength. "Kids do not get that ability [back with] Duchenne. Nothing ever returns. When you lose it, it's gone."

Advocates understand that eteplirsen is not a cure-all for Duchenne muscular dystrophy. But it's a start for a condition that has no cure. Joseph Gulfo, a biopharmaceutical expert and outspoken critic of the FDA drug approval process, believes that eteplirsen could be used in conjunction with other drugs, either on the market or on the horizon, similar to antiretroviral therapy (ART) for people living with HIV.

"These rare diseases, no one drug is going to cure [them]," Gulfo, a doctor and professor at Fairleigh Dickinson College who specializes in cancer biology, told me. "The best way to get combination therapy is to get these drugs on the market, provided they're safe and they're shown to do something. Then you have the ability to really, really make things better."

Dayna has faith that Sarepta will prove eteplirsen's benefits. She doubts the drug will be recalled; after all, she says, her son and the other boys are proof that it works. But she knows anecdotal evidence is not always enough. Still, eteplirsen's approval has opened the door for future drug development, Dayna says. It may incentivize more investors to back other experimental treatments that could work at least as well, if not better, than eteplirsen.

"I just need time," she says. "Twenty years from now, I really do believe there will be a regimen that these kids will get. I just hope we make it in time."